General options of Toolbox provide opportunity to change the settings of the following sections of the programme:
o Gap filling
In the main section there are settings available related to the organization of the data matrix and the chemical browser.
User could change the size of the cells and font of the text in the data matrix (Figure 1 – point 1). The user also could change the number of columns in the chemical browser which appear for example in the Profile Statistic mode (Figure 1 –point 2). Example illustrating this option is presented in the Figure 2.
Another option related to the way of displaying the chemicals on the data matrix. It is also related to the chemical information available for a specific structure. User is allowed to select whether to work with accounting the stereo information of the chemical structures or not (Figure 3).
1. If the 2D option is selected - stereo information for a chemical structure is not displayed on the data matrix and this type of information is not taken into account in the processes of profiling, categorization and others.
2. If 2.5D mode is checked the stereo information of the chemicals structures is displayed on the data matrix and it is taken into account.
Figure 4 illustrates the structure of Estradiol in 2D and 2.5D mode.
Note: The Toolbox needs to be restarted in order to use the newly selected option.
The options under the Database section (Figure 5) showing the folder of Toolbox database and saved (Q)SAR models.
1. If the Local connect option is checked Toolbox with the database (FDB file) stored in the same PC, where the Toolbox is installed. The installation of the database is accomplished during the process of Toolbox installation. Here the user is provided the possibility to change the working FDB file.
2. If the remote connect option is selected the Toolbox connects to a server to use its database.
3. The Folder for user models is one of the important items in this window. The user could follow this path to the folder where the user-created (Q)SAR models are saved (stored). The user is allowed to change that directory.
Three options related to the calculations of 2D and 3D parameters are illustrated in the figure (Figure 6) below.
1. The option Do not use parameter cache provides possibility to perform calculation of 2D and 3D parameters without using values calculated in advance and stored in the Toolbox cache. The user should be careful when this option is cheeked, because the process of calculations could be extremely slow in some cases.
2. Each calculator has own memory cache for calculated values. Here the user can adjust the size for these caches.
3. This option is responsible for the number of tautomers generated for the specific structure which are subject to profiling and 2D and 3D calculation. The user could change the threshold for the number of tautomeric forms which will be subject of calculations and profiling.
The options related to the way of displaying the data values collected from the Toolbox databases on the data matrix are presented in the Figure 7. See the example below (Figure 8).
The Modules panel contains list with all modules available in Toolbox – Calculators, Databases, Inventories, Profilers, (Q)SAR models, Metabolism etc. (Figure 9).
Double click on the small triangle expand an individual list of modules (Figure 9). For example double click on the calculators provides two list with all 2D and 3D calculators available in Toolbox (1).
The next figure (Figure 10) represents the node Calculators in more detail:
1. A click on each of the calculators provides more detailed information about the selected calculator (module) such as: short description, author, donator etc.
2. The button Define new calculator provides the user with the possibility to define a custom calculator and to use it within Toolbox system.
2.1. Define new calculator
In this section is presented the procedure of definition a
new custom calculator for experimental logKow values. For this purpose user
should prepare external text file with the following structure:
The structure of the needed text file is presented on the snapshot below (Figure 11).
Steps for implementing of the external file with experimental data for defined parameter into Toolbox are illustrated on the Figure 12:
1. Define the name of the new calculator
2. Define the Units of the parameter.
Note: When external file with logKow values is used there is no need to define the units due to the physical meaning of the parameter.
3. Define the type of the parameter - 2D or 3D
4. Load the external experimental data described as a tab delimited file. The process of loading is time consuming due to the big size of the file, please wait.
5. User could set an alternative calculator, in case of missing structures in the custom calculator. Alternatively this option could remain empty in which case the structures not available in the text file will not have their logKow values calculated.
6. There is also an option related to the alternative calculator. User is allowed to select between three options:
o Use only calculated values (calculated by the Toolbox implemented calculators)
o Use only values from the custom calculator
o Use values from custom file and calculated values
Note: After defining the external calculator please restart the Toolbox in order to add it in the list of calculators (Figure 13).
The newly defined calculator could be used as a descriptor in the X axis (Figure 14). Additional explanation about the procedure for activation of the new descriptor is available in the Data gap filling section of the help.
2.2. Export/Import a user defined (Q)SAR model
2.2.1. Export a user defined (Q)SAR model:
The export functionality provides the possibility to export a (Q)SAR model generated by Toolbox and transfer it to a Toolbox installation on another PC.
The procedure for export of a user defined (Q)SAR model is illustrated in the three figures below.
1. Expand the (Q)SAR models list by double click
The next steps of the procedure are illustrated in the Figure 16.
1. Find the already saved (Q)SAR model in the list and select it
2. Click on the Export button
Note: model consists of four files which are packed in one zip file during the process of export. The final steps for saving the model are presented in the next figure (Figure 17).
1. Browse the folder to save the exported model; write down the name of the file; Click Save
1. Click OK on the appeared message (Fig 18). The exported model could be imported and used within Toolbox installed on another PC.
2.2.2 Import a user defined (Q)SAR model: Within the (Q)SAR modules section resides the functionality which enables the user to import a (Q)SAR model created by Toolbox.
Expand the (Q)SAR models list by double click as it was shown in the previous sub-section Export a user defined (Q)SAR model (Figure 15). The next steps are illustrated in the following figures (Figures 19 - 21)
1. Click Import button
2. Browse the zip file for import
3. Click Open
4. Click OK to close the message
Note: The new (Q)SAR is imported successfully and will appear after a Toolbox restart.
This panel gives the user the possibility to select the preferred display unit for the different measurements presented in the data matrix and data gap filling panels (Figure 22). The left part of the panel is related with the units displayed on the data matrix (1) and the right part is related with the units used during the data gap filling process (2). In this panel also houses the Edit scale definition button (3) which is part of the definition for categorical data stored in the Toolbox databases.
The user could set different default units for each specific measurement, for example Temperature using the following procedure (Figure 23):
1. From the drop-down menu in the data matrix part of the window select Temperature, the default unit is degree Celsius.
The next steps are illustrated in the Figure 24:
2. Change it to Kelvin by selecting the radio button
3. Click OK to confirm the change
Note: The same procedure could be applied for changing the units used in the Data gap filling.
Example for the default and changed units is presented in the Figure 25:
3.1 Edit Scale definition
Some of the endpoints stored in the Toolbox databases are quantitative and the results for them are represented as categorical data. For example Skin sensitization is quantitative endpoint. The data for skin sensitization potential of the chemicals usually has different authors which have coded data in different ways – for example: John Moore University of Liverpool – Strongly sensitizing, Moderately sensitizing etc.; European center for Ecotoxicology and Toxicology of chemicals – Positive, Negative and Equivocal.
All data for one quantitative endpoint could be unified by using scale definitions. A click on the Edit scale definition… button opens a Scale definition window.
In the Scale list tab are available (see Figure 26): list with the quantitative end points in Toolbox and their associated scales (1). For some of the end points there is a default scale defined and these scales are displayed using bold font (2). In the right-hand part of the window there is more detailed information about the scales (3) such as: scale name, type, family, scale members and short description. Over the list with the different scales there are three buttons (4) for definition of a new scale, load and save of already defined scales.
The procedure for defining of a new scale is as follows (see Figure 27):
1. Click on the New button
2. Right the name of the new scale
3. Select the type of the scale:
o Nominal – there is no hierarchy between the members of the scale
o Ordinal – there is hierarchy between the members of the scale
o Ratio – Ratio scale variable is a measurement where the difference between two values is meaningful and also has a clear definition of 0.0
4. Select the family of the scale – the scale family associated with the end point. The scales belonging to the same family could be converted to each other. Here it is important to note than it is possible only to convert more informative scales to less informative.
5. Type in a member of the scale
6. Add each of the scale members
7. By using the up and down arrow the user is able to re-arrange the members in a hierarchical order.
8. The user could also write a short description about the scale.
9. Finally to confirm the created scale click Save & Close button.
3.2. Scale conversion
Besides the possibility to create a new custom scale in the Toolbox also implements functionality for definition of conversions between scales (Figure 28).
Note: Only scales belonging to the same family could be converted to each other. Also it is more reasonable to convert more informative scale to a less informative.
1. Switch to the Scale conversions tab
2. Click on the New button
3. Write the name of the new scale conversion
4. From the drop-down menu select Source scale, for this example it is the Carcinogenicity II (ISSCAN) which is the more informative scale
5. Select Destination scale - Carcinogenicity I (ISSCAN) which is the less informative scale
6. From the list with members of the source scale specific members by click. In case 2 or more members are desired for selection it is needed to keep pressed Ctrl button and click on the scale member. Select members of the Destination scale which corresponds to the already selected members of the source scale
7. Click Add
8. The newly defined transformation appears in the Conversions box
9. After finishing with definition of the all transformations click Save & Close button
This section contains three options related to the profiling (caching of results) process (Figure 29).
1. Timeout – here the user could increase or decrease the default maximum time for profiling of a structure.
Note: The profiling of some big and complex structure could take a lot of time which is the reason the timeout option was implemented. In case the time for profiling of that type of structures exceeds the set time the profiling result for these structures is !Timeout.
2. Reprofile timeout structures – this option is related to the previous. It allows the profiling the Time out structures if the Timeout threshold had been increased.
3. Do not use profiling cache – check this to turn off the usage of the Toolbox cache with regards to the profiling results. It pertains to the reading of results - it will still write the results after profiling. The user should be careful when selecting not to use the cache as the process of profiling of large sets of chemicals is quite slow. This also affects the categorization process as it relies on the stored profiling results cache.
Note: Selecting of this option is recommended is cases when check the results of newly created profiling scheme or check modifications of already existing scheme.
5. Gap filling
The gap filling window contains options related to the Data gap filling stage of the Toolbox workflow – Read-across, Trend analysis and (Q)SAR models (Figure 30).
1. General section contains options related to the descriptors used in the gap filling process.
2. Data consistency criteria panel contains all meta-data stored in the Toolbox data bases. It defines the fields used in the metadata consistency check prior to entering the data gap filling module
3. Accept prediction - In this panel the user could select which messages to appear when he/she accepts a predicted value.
In this section are placed the options related to the report generated for a prediction (Figure 31).
1. In the General panel using the options under the When the reporting chemical lists, display detailed info for user could select for how many of the category members used for accomplishing the prediction he/she wants to see a detailed information in the report.
2. In case the option When reporting additionally eliminated values is checked the report will have information which chemicals were removed from the category by using water solubility filter and filter by test conditions during the data gap filling process.
3. The option under the Accept prediction section provides possibility to change the template used for the report.
4. In the Profiling section user could select the profiling schemes for which he/she wants to see results in the report.
5. In the Data matrix section user could navigate through the data tree and select endpoints for which wants to have values exported in the report.